Opium alkaloid noscapine is an antitumor agent that arrests metaphase and induces apoptosis in dividing cells.
An alkaloid from opium, noscapine, is used as an antitussive drug and has low toxicity in humans and mice. We show that noscapine binds stoichiometrically to tubulin, alters its conformation, affects microtubule assembly, and arrests mammalian cells in mitosis. Furthermore, noscapine causes apoptosis in many cell types and has potent antitumor activity against solid murine lymphoid tumors (even when the drug was administered orally) and against human breast and bladder tumors implanted in nude mice. Because noscapine is water-soluble and absorbed after oral administration, its chemotherapeutic potential in human cancer merits thorough evaluation.
Ye
K
K
Graduate Program in Biochemistry and Molecular Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Ke
Y
Y
Keshava
N
N
Shanks
J
J
Kapp
J A
JA
Tekmal
R R
RR
Petros
J
J
Joshi
H C
HC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D053938:DNA Fragmentation; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008677:Metaphase / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000378:metabolism; D009665:Noscapine / Q000494:pharmacology*; D011487:Protein Conformation / Q000187:drug effects; D013945:Thymoma / Q000188:drug therapy; D014404:Tubulin / Q000378:metabolism
D000970:Antineoplastic Agents; D014404:Tubulin; D009665:Noscapine